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1.
J Transl Genet Genom ; 5: 200-217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34622145

RESUMO

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. Results: We discovered positive associations between FROH and CLL (ß = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (ß = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (ß = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

2.
J Athl Train ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404092

RESUMO

CONTEXT: Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a bat or racket to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested. OBJECTIVE: To determine if a history of participation in racket or bat sports is associated with the prevalence of thumb-base osteoarthritis. DESIGN: Descriptive epidemiology study. SETTING: Osteoarthritis Initiative. Four clinical sites in the United States. PARTICIPANTS: We included men and women from the recruited from the community. Eligible participants had dominant hand radiographic readings, hand symptom assessments, and historical physical activity survey data. MAIN OUTCOME MEASURES: A history of exposure to racket or bat sports (baseball/softball, racquetball/squash, badminton, table tennis, tennis [doubles/singles]) was based on self-reported recall data covering 3 age ranges (12-18 years, 19-34 years, 35-49 years). Prevalent radiographic thumb-base osteoarthritis was defined as someone with Kellgren-Lawrence grade≥2 in the first carpometacarpal joint or scaphotrapezoidal joint at the OAI baseline visit. Symptomatic thumb-base osteoarthritis was defined as the presence of radiographic osteoarthritis and hand/finger symptoms. RESULTS: In total, we included 2309 participants. Among 1049 men, 355 (34%) and 56 (5%) had radiographic or symptomatic thumb-base osteoarthritis, respectively; and among 1260 women, 535 (42%) and 170 (13%), respectively. After adjusting for age, race, and education level, we found no statistically significant associations between a history of any racket or bat sport participation and thumb-base osteoarthritis (radiographic or symptomatic; odds ratios range from 0.82 to 1.34). CONCLUSIONS: Within a community-based cohort, a self-reported history of participation in racket or bat sports was not associated with an increased odds of having radiographic or symptomatic thumb-base osteoarthritis in the dominant hand.

4.
Am J Epidemiol ; 190(10): 1977-1992, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33861317

RESUMO

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948-2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.


Assuntos
Estudos de Associação Genética/métodos , Fenômica/métodos , Medicina de Precisão/métodos , Agregação de Dados , Humanos , Disseminação de Informação , National Heart, Lung, and Blood Institute (U.S.) , Fenótipo , Avaliação de Programas e Projetos de Saúde , Estados Unidos
6.
J Clin Endocrinol Metab ; 106(7): e2567-e2579, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33754148

RESUMO

CONTEXT: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. OBJECTIVE: We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI). METHODS: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use. RESULTS: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%; 95% CI, -2.81% to -0.78%) or monocarboxynonyl phthalate (-1.84%; 95% CI, -2.80% to -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change. CONCLUSION: Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.


Assuntos
Monitoramento Biológico , Densidade Óssea , Disruptores Endócrinos/urina , Ácidos Ftálicos/urina , Pós-Menopausa/urina , Absorciometria de Fóton , Idoso , Biomarcadores/urina , Estudos de Casos e Controles , Creatinina/urina , Estudos Transversais , Exposição Ambiental/análise , Terapia de Reposição de Estrogênios , Feminino , Colo do Fêmur/diagnóstico por imagem , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/prevenção & controle , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Ossos Pélvicos/diagnóstico por imagem , Estudos Prospectivos , Fatores de Risco , Saúde da Mulher
8.
J Bone Miner Res ; 36(3): 469-479, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33249669

RESUMO

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I2 index >60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10-4 ), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10-4 ) and 7q31 (WNT16, p = 2.96 × 10-5 ), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p < 2.23 × 10-4 ), 11q14 (DCDC5, p < 5.35 × 10-5 ), and 17p13 (SMG6, p < 6.78 × 10-5 ) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10-2 ), MBL2 (p = 4.09 × 10-2 ), MEPE (p = 3.15 × 10-2 ), SLC25A13 (p = 3.03 × 10-2 ), STARD3NL (p = 3.35 × 10-2 ), and TNFRSF11A (p = 3.18 × 10-3 ) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Densidade Óssea , Lectina de Ligação a Manose , Adolescente , Adulto , Idoso , Densidade Óssea/genética , Criança , Feminino , Colo do Fêmur , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte da Membrana Mitocondrial , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
9.
Drug Alcohol Depend ; 217: 108327, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091843

RESUMO

The severity of the overdose epidemic underscores the urgent need for innovative and high impact interventions that promote the rapid penetration and scale up of evidence-based practices (EBPs) in communities profoundly affected by fatal opioid overdose. This special issue shares scientific advancements in implementation research design and evaluation of a novel data-driven community-based intervention. The HEALing (Helping End Addiction Long-Term) Communities Study (HCS) is a four-year study that is designed to examine the effectiveness of the Communities That HEAL (CTH) intervention. The CTH intervention supports the dissemination of EBPs in 67 communities across four high-burdened states-Kentucky, Massachusetts, New York, and Ohio. The diversity in these communities in terms of rural-urban status, race-ethnicity and other social determinants of health facilitates generalizability of results to other communities across the US. The nine papers in this special issue describe critical elements that constitute the HCS framework and design. This includes the implementation of EBPs that have a substantial impact on fatal and non-fatal opioid overdose, the Opioid-overdose Reduction Continuum of Care Approach, communication campaigns to increase awareness and demand for EBPs and reduce stigma against people with OUD and MOUD interventions, and the process of community engagement. This includes how to form community coalitions and gain their commitment, and steps taken to mobilize coalitions to pursue EBP implementation and ensure EBPs are adapted for community needs. The collective papers in this issue demonstrate that the design of any complex study must adapt to unanticipated temporal events, including the rapidly emerging COVID-19 crisis. Readers will learn about the scientific process of the design and implementation of a community-engaged intervention, its methodologies, guiding conceptual models, and research implementation strategies that can be applied to address other health issues.


Assuntos
COVID-19/epidemiologia , Serviços de Saúde Comunitária/métodos , Prática Clínica Baseada em Evidências/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Terapia Comportamental/métodos , COVID-19/psicologia , Serviços de Saúde Comunitária/tendências , Overdose de Drogas/diagnóstico , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controle , Prática Clínica Baseada em Evidências/tendências , Humanos , Transtornos Relacionados ao Uso de Substâncias/psicologia
10.
JAMA Intern Med ; 180(9): 1232-1240, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32730575

RESUMO

Importance: Repeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture. Objective: To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone. Design, Setting, and Participants: The Women's Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019. Main Outcomes and Measures: Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up. Results: Of 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score. Conclusions and Relevance: The findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.


Assuntos
Densidade Óssea , Fraturas do Quadril/epidemiologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Medição de Risco , Fatores de Tempo , Estados Unidos
12.
J Clin Transl Sci ; 4(2): 102-107, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32313699

RESUMO

Background: In order to conduct translational science, scientists must combine domain-specific expertise with knowledge on how to identify and cross translational hurdles, and insights on positioning discoveries for the next translational stage. Expert educators from the Clinical and Translational Science Awards (CTSA) Consortium identified 97 knowledge, skills, and abilities (KSAs) important to include in training programs for translational scientists. To assist educators and trainees to use these KSAs, a conceptual model called "Personalized Pathways" was developed that prioritizes KSAs based on trainee background, research area, or phenotype, and expertise on the research team. Purpose: To understand how CTSA educators prioritize specific KSAs when developing personalized training plans for different translational phenotypes and to identify areas of similarity and difference across phenotypes. Methods: A web-based, cross-sectional survey of CTSA educators was done. For a selected phenotype, respondents recommended one of four levels of mastery for each of the 97 KSAs. Results were tabulated by frequency, weighted by importance, and divided into tertiles representing high, middle, and lower priority KSAs. Agreement across phenotypes was compared using Krippendorff's alpha. Results: Ten KSAs were high training priority for Preclinical, Clinical, and Community-Engaged phenotypes. These address research methods, responsible conduct of research, team building, and communicating research results. Nine KSAs were in the next tertile for priority reflecting KSAs in biostatistics, bioinformatics, regulatory precepts, and translating implications of research findings. Conclusion: A smaller set of KSAs can be prioritized for training Preclinical-, Clinical-, and Community-Engaged researchers. Future work should explore this approach for other phenotypes.

13.
Oncologist ; 25(8): 712-721, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32250503

RESUMO

BACKGROUND: Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. MATERIALS AND METHODS: In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. RESULTS: Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). CONCLUSION: These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. IMPLICATIONS FOR PRACTICE: Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.


Assuntos
Hipertensão , Neoplasias , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Estudos Prospectivos , Resultado do Tratamento , Saúde da Mulher
15.
J Foot Ankle Res ; 13(1): 11, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131869

RESUMO

BACKGROUND: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus. METHODS: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses. RESULTS: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family. CONCLUSION: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology.


Assuntos
Canais de Cloreto/genética , Hallux Valgus/etnologia , Hallux Valgus/genética , Polimorfismo de Nucleotídeo Único/genética , /genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 1/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Locos de Características Quantitativas/genética
16.
Gait Posture ; 77: 175-181, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32044697

RESUMO

BACKGROUND: Suboptimal patient-reported function and movement impairments often persist after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Individuals with FAIS with preoperative cartilage pathology (ie. chondropathy) demonstrate distinct movement patterns and have worse post-operative outcomes. It is unknown whether the presence of chondropathy after surgery negatively affects movement and function. RESEARCH QUESTION: Do sagittal plane gait mechanics differ based on chondropathy severity following arthroscopy for FAIS? METHODS: A cross-sectional walking gait analysis was performed for 25 participants post-arthroscopy (2.48 ±â€¯1.38y) and 12 healthy controls (HCs). Peak total support moment (TSM) and relative contributions of the hip, knee, and ankle were calculated during loading response. The Hip Osteoarthritis MRI Scoring System was used to categorize the FAIS group into no-mild or moderate-severe chondropathy groups based on 3 T magnetic resonance imaging of their surgical hip. The interactions of group by limb were evaluated for kinetic variables, covaried by gait speed. RESULTS: Groups did not differ based on age, BMI and sex distribution (P ≥ 0.14). 13 participants with FAIS presented with moderate-severe chondropathy and 12 presented with no-mild chondropathy. Participants with moderate-severe chondropathy walked significantly slower than both other groups (P = 0.006) and demonstrated lower peak TSM than those with no-mild chondropathy (P = 0.002). Participants with no-mild chondropathy demonstrated lower hip (61.5 %) and greater ankle (17.7 %) contributions to the TSM on the involved limb compared to the moderate-severe group (hip:73.4 %, P = 0.07; ankle:10.5 %, P = 0.007). SIGNIFICANCE: Slower gait speed alone did not explain the lower TSM strategy in participants with moderate-severe chondropathy. Interestingly, the joint contribution strategy of this group was not different than HCs. Participants with no-mild chondropathy demonstrated a TSM strategy that shifted the demand away from their hip and toward their ankle. Given the small sample size, and large variability in joint strategies, future work needs to examine whether these alterations in gait strategy, with or without advanced chondropathy, impact patient function.


Assuntos
Artroscopia , Cartilagem Articular/patologia , Impacto Femoroacetabular/cirurgia , Marcha/fisiologia , Adolescente , Adulto , Fenômenos Biomecânicos , Cartilagem Articular/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Impacto Femoroacetabular/patologia , Impacto Femoroacetabular/fisiopatologia , Articulação do Quadril/patologia , Articulação do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
18.
Bone ; 134: 115222, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31911206

RESUMO

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.


Assuntos
Conservadores da Densidade Óssea , Ácido Etidrônico , Osteíte Deformante , Osteoporose Pós-Menopausa , Osteoporose , Densidade Óssea , Conservadores da Densidade Óssea/história , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos , Ácido Etidrônico/história , Ácido Etidrônico/uso terapêutico , Feminino , História do Século XX , História do Século XXI , Humanos , Masculino , Osteoporose/tratamento farmacológico
19.
J Clin Transl Sci ; 4(6): 556-561, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-33942017

RESUMO

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.

20.
PM R ; 12(6): 529-537, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31628825

RESUMO

BACKGROUND: To date, there have not been any epidemiologic studies that have evaluated the association between swimming over a lifetime and knee health. OBJECTIVE: The study aimed to evaluate the relationship of a history of swimming with knee pain, radiographic knee OA (ROA), and symptomatic knee OA (SOA). DESIGN: Cross-sectional retrospective study. SETTING: Four academic centers in the United States. PARTICIPANTS: Respondents to the historical physical activity survey within the Osteoarthritis Initiative with knee radiographs and symptom assessments. METHODS: In this retrospective study nested within the Osteoarthritis Initiative, researchers performed logistic regression with the predictor being swimming over a lifetime and over particular age ranges. MAIN OUTCOME MEASUREMENTS: Person-based definitions of frequent knee pain, ROA, and SOA. RESULTS: A total of 2637 participants were included, with a mean age of 64.3 years (SD 8.9), body mass index of 28.4 kg/m2 (SD 4.9), and 44.2% male. Over a lifetime, the adjusted prevalence measures for frequent knee pain, ROA, and SOA for any versus no history of swimming were 36.4% (33.4% - 39.5%) v. 39.9% (37.4% - 42.5%), 54.3% (51.0% - 57.6%) v. 61.1% (58.4% - 63.7%), and 21.9% (19.4% - 24.7%) v. 27.0% (24.7% - 29.4%) respectively. CONCLUSIONS: This is the first epidemiologic study to indicate that swimming is potentially beneficial toward knee health, particularly when performed earlier in life (before age 35). Future prospective studies are needed to confirm these findings and to better scrutinize the associations in older age groups.


Assuntos
Osteoartrite do Joelho , Natação , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
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